The three established breast cancer expression biomarkers—estrogen receptor (ER), progesterone receptor (PR), and HER2—are discordant between the primary tumor and the residual tumor after neoadjuvant therapy in 5–40% of cases that do not achieve a pathologic complete response (pCR, defined as absence of remaining invasive cancer)5,6. The gene discussed is ESR1; the disease is breast carcinoma.